NEUROBIOLOGICAL EFFECT OF LONG-TERM ESTROGEN REPLACEMENT

描述（由申请人提供）：本指导性患者导向研究 职业发展奖提案包含教学课程，指导 指导，以及旨在应用这些原则的临床研究项目 学研究者的临床研究兴趣在于整合 生殖内分泌学与认知、衰老和大脑功能的关系 和神经化学拟议的临床培训和研究， 此应用程序旨在提高她在研究设计方面的技能， 生物统计学、认知神经科学和神经成像技术， 最终目标是成为一名独立的临床研究者。的 K30临床研究培训补助金的课程，导致硕士 临床研究设计和统计分析科学，是 包括在课程中。研究计划的目的是研究 健康绝经后妇女长期激素治疗的神经生物学效应 妇女将招募60名60岁或以上的绝经后女性， 这项横断面研究（20名从未使用过激素，20名将使用激素） 使用雌激素至少10年，20年将使用雌激素， 至少10年）。所有女性都将接受广泛的 神经心理学测试电池，单光子发射计算 用胆碱能突触末端标记物进行断层扫描（SPECT） 密度、解剖磁共振成像（MRI）和雌二醇测量 和雌酮。每组10名女性也将接受功能性磁共振成像 （功能磁共振成像）在一个认知任务，旨在激活受影响的大脑区域， 雌激素并在阿尔茨海默病中发生变化。组间比较将 更深入地了解激素治疗对大脑的影响， 神经化学和认知。

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award proposal contains didactic coursework, mentored instruction, and a clinical research project designed to apply the principles learned. The investigators' clinical research interest is in the integration of reproductive endocrinology with cognition, aging, and brain function and neurochemistry. The proposed clinical training and research studies in this application are designed to increase her skills in study design, biostatistics, cognitive neurosciences and neuroimaging techniques, with the ultimate goal of developing into an independent clinical investigator. The curriculum of the K30 Training Grant in Clinical Research, leading to a Master of Science in Clinical Research Design and Statistical Analysis at the UM, is included in the coursework. The goal of the research proposal is to study the neurobiological effects of long-term hormone therapy in healthy postmenopausal women. Sixty postmenopausal women, 60 years or older, will be recruited for this cross-sectional study (20 will never have used hormones, 20 will have used estrogen only for at least 10 years, and 20 will have used estrogen and progestin for at least 10 years). All women will undergo an extensive neuropsychological testing battery, a single photon emission computed tomography (SPECT) scan with a marker of cholinergic synaptic terminal density, an anatomic magnetic resonance image (MRI), and measures of estradiol and estrone. Ten women from each group will also undergo a functional MRI (fMRI) during a cognitive task designed to activate brain areas affected by estrogen and altered in Alzheimer's Disease. Comparison between groups will offer a greater understanding of the effect of hormone therapies on brain neurochemistry and cognition.